Modeling the Onset of Senescence-Associated Secretory Phenotype Predicts Therapeutic Targets

The 2018 study "Modeling the onset of senescence associated secretory phenotype predicts therapeutic targets" focused on cellular senescence, a state of permanent cell cycle arrest that can protect against malignant transformation but also drive aging and age-related disorders. Senescent cells often release a variety of soluble factors, known as the senescence associated secretory phenotype (SASP), which can spread senescence within tissues and organs and promote age-associated disorders, including skin aging and impaired chronic wound healing. The researchers developed a Boolean network model-based gene regulatory network of SASP and simulated the network to inhibit SASP during DNA damage induced senescence. This simulation allowed them to predict different in-silico gene knockouts that can prevent damaging effects of key SASP-factors. The most promising in-silico knockout candidate was NF-κB Essential Modulator (NEMO) or IKK-γ. In vitro experiments in murine dermal fibroblasts confirmed the importance of NEMO to successfully inhibit key SASP following DNA-damage, suggesting potential therapeutic targets for SASP-associated aging diseases.